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Talimogene laherparepvec (TVEC) is a genetically modified herpes simplex virus-1 approved as an intralesional oncolytic immunotherapy for the treatment of advanced melanoma. Cutaneous reactions at the site of injection may mimic recurrent or progressive melanoma; histopathological findings have included chronic granulomatous dermatitis, neutrophilic dermatitis, lymphocytic dermatitis, and pigment incontinence. We report a 39-year-old male with metastatic stage IIIc melanoma treated with TVEC with clinical regression of melanoma lesions that later developed pink nodules at sites of prior injection. Histopathology demonstrated a nodular mononuclear infiltrate that stained strongly and diffusely with CD45 and CD20 with a surrounding rim of CD3-positive T-cells. Immunoglobulin gene rearrangement was negative for a clonal B-cell population. To our knowledge, this is the first report of a pseudolymphomatous reaction mimicking recurrent melanoma after TVEC therapy.

The NCCN Guidelines for Breast Cancer include up-to-date guidelines for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget disease, phyllodes tumor, inflammatory breast cancer, male breast cancer, and breast cancer during pregnancy. These guidelines are developed by a multidisciplinary panel of representatives from NCCN Member Institutions with breast cancer–focused expertise in the fields of medical oncology, surgical oncology, radiation oncology, pathology, reconstructive surgery, and patient advocacy. These NCCN Guidelines Insights focus on the most recent updates to recommendations for adjuvant systemic therapy in patients with nonmetastatic, early-stage, hormone receptor–positive, HER2-negative breast cancer.

BackgroundConcurrent germline (g) pathogenic variants related to hereditary breast cancer represent a rare occurrence. While double heterozygosity in gBRCA1 and gBRCA2 has been reported in the past, herein we describe the first case of three known concurrent pathogenic variants identified in a family with a strong history of breast cancer.Case presentationThe proband is a 55-year-old female diagnosed with synchronous bilateral breast cancers. She underwent a multi-gene panel testing indicating the presence of 3 concurrent heterozygous germline deleterious variants inBRCA1(c.181T > G), BRCA2 (c.4398_4402delACATT), and CHEK2 (1100delC). The patient’s two daughters (34 and 29 years-old) were found to be transheterozygous for inherited pathogenic variants in BRCA1(c.181T > G)and CHEK2(1100delC)genes.ConclusionThe cancer risk and phenotypic manifestations associated with transheterozygous or multiple concurrent deleterious germline variants in hereditary breast cancer requires further investigation. A personalized approach to counseling, screening, and risk reduction should be undertaken for these individuals.

Leptin influences inflammation and tumor growth and leptin signaling is often dysregulated among obese breast cancer survivors. This leads to a lack of satiety and, ultimately, risk for further weight gain. Breast cancer survivors also experience high rates of depression and anxiety, which are linked to leptin production. This study examined how a woman’s anxiety and depressive symptoms, in combination with their obesity status, were associated with leptin. Breast cancer survivors (n = 200, stages 0–IIIa) completed a baseline visit before treatment and two follow-up visits, 6 and 18 months after treatment ended. Women completed anxiety and depression measures, and blood samples provided leptin data at each visit. This study related fluctuations in a survivor’s own depression and anxiety (i.e., within-person effects), as well as average effects of depression and anxiety (i.e., between-person effects) to changes in leptin depending on BMI. Obese survivors’ leptin was significantly higher at visits when they had higher anxiety and depression symptoms than their own average level of symptoms. In contrast, within-person fluctuations in depression and anxiety were not related to leptin levels among non-obese survivors. No significant between-person effects of depression or anxiety on leptin emerged. Leptin is a critical risk factor for recurrence and further health consequences. Our findings highlight how psychological health influences leptin production among breast cancer survivors. These results highlight a biological pathway that may facilitate further weight gain and health risks among distressed, obese breast cancer survivors.

Objective Breast cancer survivors who experience psychological and physical symptoms after treatment have an increased risk for comorbid disease development, reduced quality of life, and premature mortality. Identifying factors that reduce or exacerbate their symptoms may enhance their long-term health and physical functioning. This study examined how survivors' marital status and marital satisfaction-key health determinants-impacted their psychological and physical health trajectories to understand when, and for whom, marriage offers health benefits. Methods Breast cancer survivors (n=209, stages 0-IIIC) completed a baseline visit before treatment and two follow-up visits 6 and 18 months after treatment ended. Women completed questionnaires assessing their marital status and satisfaction when applicable, as well as their psychological (depressive symptoms, stress) and physical (fatigue, pain) health at each visit. Results Married women-both those in satisfying and dissatisfying marriages-experienced improvements in their depressive symptoms, stress, and fatigue from pretreatment to 6- and 18-months posttreatment. Unmarried (i.e., single, divorced/separated, or widowed) women's depressive symptoms, stress, fatigue, and pain did not change over time, instead remaining elevated 6 and 18 months after treatment ended. Women in satisfying marriages also had fewer psychological and physical symptoms after treatment than those who were unmarried or in dissatisfying marriages. Conclusions Although marriage was associated with improved psychological and physical health, the gains were most notable when survivors' marriages were satisfying. Thus, the quality of survivors' marriages, rather than the marriage itself, provided the most benefits to their psychological and physical health. This article is protected by copyright. All rights reserved.

IntroductionNipple-sparing mastectomy (NSM) can be performed for the treatment of breast cancer and risk reduction, but total mammary glandular excision in NSM can be technically challenging. Minimally invasive robot-assisted NSM (RNSM) has the potential to improve the ergonomic challenges of open NSM. Recent studies in RNSM demonstrate the feasibility and safety of the procedure, but this technique is still novel in the USA.Methods and analysisThis is a single-arm prospective pilot study to determine the safety, efficacy and potential risks of RNSM. Up to 12 RNSM will be performed to assess the safety and feasibility of the procedure. Routine follow-up visits and study assessments will occur at 14 days, 30 days, 6 weeks, 6 months and 12 months. The primary outcome is to assess the feasibility of removing the breast gland en bloc using the RNSM technique. To assess safety, postoperative complication information will be collected. Secondary outcomes include defining benefits and challenges of RNSM for both surgeons and patients using surveys, as well as defining the breast and nipple-areolar complex sensation recovery following RNSM. Mainly, descriptive analysis will be used to report the findings.Ethics and disseminationThe RNSM protocol was reviewed and approved by the US Food and Drug Administration using the Investigational Device Exemption mechanism (reference number G200096). In addition, the protocol was registered with ClinicalTrials.gov (NCT04537312) and approved by The Ohio State University Institutional Review Board, reference number 2020C0094 (18 August 2020). The results of this study will be distributed through peer-reviewed journals and presented at surgical conferences.Trial registration numberNCT04537312.

Background This study evaluates the association of adjuvant radiation therapy (RT) with improved locoregional (LR) recurrence for resected melanoma satellitosis and in-transit disease (ITD). Materials and Methods Data were collected retrospectively for resected melanoma satellitosis/ITD from 1996 to 2017. Results 99 patients were identified. 20 patients (20.2%) received adjuvant RT while 79 (79.8%) did not. Mean follow-up in the RT group was 4.3 years and 4.7 years in the non-RT group. 80% of patients who underwent RT suffered a complication, most commonly dermatitis. Locoregional recurrence occurred in 9 patients (45%) treated with adjuvant RT and 30 patients (38%) in the non-RT group ( P = 0.805). Median LR-DFS was 5.8 years in the RT group and 9.5 years in the non-RT group ( P = 0.604). On multivariable analysis, having a close or positive margin was the only independent predictor of LR-DFS (HR 3.8 95% CI 1.7-8.7). In-transit disease was associated with improved overall survival when compared to satellitosis (HR 0.260, 95% CI 0.08-0.82). Discussion The use of adjuvant RT is not associated with improved locoregional control in resected melanoma satellitosis or ITD. Close or positive margin was the only treatment-related factor associated with decreased LR-DFS after surgical resection of satellitosis/ITD.

BACKGROUND: Prior to treatment, breast cancer patients are less physically fit compared to peers; during cancer treatment, their fitness typically declines. Depressive symptoms are associated with reduced activity up to 5 years post-treatment, but research has not identified mechanisms linking depression and lower activity. The current study assessed relationships among breast cancer patients’ depression and perceived exertion during exercise as well as heart rate, an objective indicator of exertion. METHODS: Participants were 106 breast cancer patients, stages I–IIIA, who completed surgery but had not started adjuvant treatment. Heart rate and self-rated exertion, measured using the Borg Scale of Perceived Exertion, were assessed every 2 min during a graded exercise test. Depression was assessed using the CES-D and a structured clinical interview. RESULTS: Compared to women below the CES-D clinical cutoff, women with significant depressive symptoms reported steeper increases in exertion during the exercise test (p = .010) but had similar heart rates (p = .224) compared to women below the cutoff. Major depression history was unrelated to perceived exertion (ps > .224) and heart rate (ps > .200) during exercise. CONCLUSIONS: Women with currently elevated depressive symptoms experienced exercise as more difficult compared to women below the CES-D cutoff, but these self-perceptions did not reflect actual heart rate differences. Depression may make exercise feel more demanding, which could ultimately decrease patients’ likelihood of engaging in regular exercise. Results support the use of depression screening tools following breast cancer surgery to identify and intervene on individuals at risk for decreased physical activity during survivorship.

The aim of this study was to compare wire localization (WL) and radioactive seed localization (RSL) for nonpalpable breast lesions with regard to margin status, re-excision rate, procedure length, and complications related to localization. A retrospective review of the electronic health records at a single institution was performed. There was no difference in re-excision rate, margin positivity, volume of tissue removed, and complication rate for RSL vs WL (P = 0.9934, P = 0.9934, P = 0.6645, and P = 0.4716 respectively). The only difference was a longer OR time, RSL = 104.408 minutes vs WL = 82.386 minutes. (P = 0.0163). RSL and WL are comparable techniques for localization of nonpalpable breast lesions.

Background Breast cancer survivors are prone to weakened gut barriers, allowing bacteria to migrate into the blood stream. Gut permeability fuels inflammation, which, among survivors, can elevate risk for comorbid disease development, cancer recurrence, and a poor quality of life; however, survivors’ satisfying relationships can provide health benefits. This longitudinal study used a conceptual model addressing how intimate relationships is associated with health through changes in gut permeability and inflammation. Method Breast cancer survivors (n=139, stages 0–IIIC) completed a baseline visit before treatment and two follow-up visits 6 and 18 months after treatment ended. Women who had an abnormal breast cancer test followed by a benign diagnosis completed visits within a comparable timeframe (noncancer patient controls; n=69). All women completed questionnaires assessing their relationship satisfaction and provided blood samples to assess two bacterial endotoxin biomarkers, lipopolysaccharide-binding protein (LBP) and soluble CD14 (sCD14), as well as C-reactive protein (CRP) and interleukin 6 (IL-6). Results Within-person multilevel mediation analyses showed that when a survivor’s relationship satisfaction was higher than usual, her own LBP and LBP/sCD14 were lower, which was associated with lower than her own average CRP and IL-6 (95% CIs [-0.0104, -0.0002]). IL-6 was also higher when older survivors, but not younger survivors, experienced higher than usual intestinal permeability (p=.001). These effects of satisfying relationships held after accounting for cancer-related and behavioral factors. Post-hoc analyses showed LBP, sCD14, and LBP/sCD14 were associated with CRP for the cancer survivors, but only LBP and LBP/sCD14 were linked to CRP among the noncancer control patients. Conclusion The gut environment is a new promising candidate for understanding a relationship’s long-term health impact, particularly among those with elevated health risks. Survivors may reap multiple physiological benefits from satisfying relationships.

BACKGROUND: Black breast cancer survivors have greater morbidity and mortality than White survivors. However, evidence comparing Black survivors’ psychological symptoms with their White counterparts has been mixed. Prior studies have not compared Black and White survivor’s distress-related symptom trajectories from pre- to post-treatment – the goal of the current study. METHODS: At three annual visits from shortly after diagnosis to 6 and 18 months post-treatment, 195 women (n=163 White; n=32 Black) reported their cancer-related distress (intrusive thoughts and avoidance), perceived stress, anxiety and depressive symptoms, fatigue, and pain. RESULTS: Adjusting for age, educational attainment, income, treatment type, stage at diagnosis, and physical comorbidities, Black and White breast cancer survivors had different trajectories of cancer-related distress (p=.004), intrusive thoughts about cancer diagnosis and treatment (p=.002), perceived stress (p=.04), emotional fatigue (p=.01), and vigor (p=.02). Specifically, among White women, these distress-related symptoms improved from diagnosis to 6 months post-treatment (ps.09). CONCLUSION: Longitudinal assessment of the same breast cancer survivors from diagnosis to early survivorship revealed that Black and White survivors had divergent trajectories of psychological distress symptoms that were not reliably evident at a single timepoint. Overall, White women reported less psychological distress from pre- to post-treatment, but Black women’s distress remained high from diagnosis to 18 months post-treatment. If left untreated, Black women’s high distress levels may contribute to their poorer health throughout survivorship.

Objective To assess whether preoperative ultrasound (US) assessment of regional lymph nodes in patients who present with primary cutaneous melanoma provides accurate staging. Background It has been suggested that preoperative US could avoid the need for sentinel node (SN) biopsy, but in most single-institution reports, the sensitivity of preoperative US has been low. Methods Preoperative US data and SNB results were analyzed for patients enrolled at 20 centers participating in the screening phase of the second Multicenter Selective Lymphadenectomy Trial. Excised SNs were histopathologically assessed and considered positive if any melanoma was seen. Results SNs were identified and removed from 2859 patients who had preoperative US evaluation. Among those patients, 548 had SN metastases. US was positive (abnormal) in 87 patients (3.0%). Among SN-positive patients, 39 (7.1%) had an abnormal US. When analyzed by lymph node basin, 3302 basins were evaluated, and 38 were true positive (1.2%). By basin, the sensitivity of US was 6.6% (95% confidence interval: 4.6-8.7) and the specificity 98.0% (95% CI: 97.5-98.5). Median cross-sectional area of all SN metastases was 0.13 mm; in US true-positive nodes, it was 6.8 mm. US sensitivity increased with increasing Breslow thickness of the primary melanoma (0% for ≤1 mm thickness, 11.9% for >4 mm thickness). US sensitivity was not significantly greater with higher trial center volume or with pre-US lymphoscintigraphy. Conclusion In the MSLT-II screening phase population, SN tumor volume was usually too small to be reliably detected by US. For accurate nodal staging to guide the management of melanoma patients, US is not an effective substitute for SN biopsy.

Background Among breast cancer survivors, elevated inflammation has been linked to greater recurrence risk. Psychological processes, such as cancer-related distress, can pose threats to a survivor’s longevity and wellbeing. Although distress can heighten inflammation, little is known about how fluctuations in distress during and after treatment impact a woman’s own inflammation – the primary question of this study. Methods Breast cancer survivors (n = 165, stages 0-III) completed a baseline visit before treatment and two follow-up visits 6 and 18 months after. At each visit, women completed the Impact of Events Scale to assess cancer-related distress, and a blood sample was collected to measure proinflammatory cytokines IL-6, TNF-α, IL-1β, and IL-8. This longitudinal study related fluctuations in survivor’s own cancer-related distress (i.e., within-person effects), as well as average effects of cancer-related distress between survivors (i.e., between-person effects) to inflammatory changes across visits. Results Women had elevated inflammation at visits where they expressed more cancer-related distress than what was typical. In contrast, the average cancer-related distress was not associated with inflammation. Conclusion Larger increases in a women’s cancer-related distress was linked with higher inflammation across visits. Comparing a survivor’s own cancer-related distress to her average levels may prove useful in identifying links between distress and inflammation.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on the clinical presentation and workup of suspected bladder cancer, treatment of non-muscle-invasive urothelial bladder cancer, and treatment of metastatic urothelial bladder cancer because important updates have recently been made to these sections. Some important updates include recommendations for optimal treatment of non-muscle-invasive bladder cancer in the event of a bacillus Calmette-Guerin (BCG) shortage and details about biomarker testing for advanced or metastatic disease. The systemic therapy recommendations for second-line or subsequent therapies have also been revised. Treatment and management of muscle-invasive, nonmetastatic disease is covered in the complete version of the NCCN Guidelines for Bladder Cancer available at NCCN.org. Additional topics covered in the complete version include treatment of nonurothelial histologies and recommendations for nonbladder urinary tract cancers such as upper tract urothelial carcinoma, urothelial carcinoma of the prostate, and primary carcinoma of the urethra.

PURPOSE: A number of studies have shown that self-rated health reliably predicts mortality. This study assessed the impact of perseveration on self-rated health, physical functioning, and physical symptoms (pain, fatigue, breast cancer symptoms) among breast cancer patients. We hypothesized that cancer-related distress would serve as an intervening variable between both worry and rumination and self-rated health, physical functioning, and physical symptoms. METHODS: Women (N=124) who were approximately seven weeks post-surgery but pre adjuvant treatment completed the Impact of Events Scale, the Penn State Worry Questionnaire, and the Rumination Scale. They also rated their pain, fatigue, physical functioning, and self-rated health using the RAND-36 and breast cancer symptoms with the Breast Cancer Prevention Trial Symptom Checklist (BCPT). Covariates included body mass index, age, cancer stage, menopause status, and physical comorbidities. RESULTS: Worry was associated with higher cancer-related distress, which in turn predicted greater pain and breast cancer symptoms, poorer physical functioning, and lower self-rated health. Rumination also predicted greater cancer-related distress, which ultimately contributed to greater pain along with poorer physical functioning and self-rated health. Models with fatigue as an outcome were not significant. CONCLUSIONS: These findings suggest that perseveration can heighten cancer-related distress and subsequent perceptions of physical symptoms and health among breast cancer patients prior to adjuvant treatment. Perseveration early in the cancer trajectory can adversely increase the impact of a cancer diagnosis and treatment on functioning and quality of life.

Background. Although a well-established causative relationship exists between smoking and several epithelial cancers, the association of smoking with metastatic progression in melanoma is not well studied. We hypothesized that smokers would be at increased risk for melanoma metastasis as assessed by sentinel lymph node (SLN) biopsy.Methods. Data from the first international Multicenter Selective Lymphadenectomy Trial (MSLT-I) and the screening-phase of the second trial (MSLT-II) were analyzed to determine the association of smoking with clinicopathologic variables and SLN metastasis.Results. Current smoking was strongly associated with SLN metastasis (p = 0.004), even after adjusting for other predictors of metastasis. Among 4231 patients (1025 in MSLT-I and 3206 in MSLT-II), current or former smoking was also independently associated with ulceration (p Conclusion. The direct correlation between current smoking and SLN metastasis of primary cutaneous melanoma was independent of its correlation with tumor thickness and ulceration. Smoking cessation should be strongly encouraged among patients with or at risk for melanoma.

Timing of surgical resection after breast cancer diagnosis is dependent on a variety of factors. Lengthy delays may lead to progression; however, the impact of modest delays is less clear. The aim of this study was to evaluate the impact of surgical timing on outcomes, including disease-free survival (DFS) and nodal status (NS). The cancer registry from one academic cancer hospital was retrospectively reviewed. Time from initial biopsy to surgical resection was calculated for patients with ductal carcinoma in situ (DCIS) and stage 1 and 2 invasive carcinomas. Early (0-21 days), intermediate (22-42 days), and late (43-63 days) surgery groups were evaluated for differences in NS and DFS for each cancer stage separately. A total of 3,932 patients were identified for analysis. There were no differences in DFS noted for DCIS. For stage 1, early surgery (ES) was associated with worse DFS compared to intermediate surgery (IS) (p = 0.025). There were no significant differences between ES and late surgery (LS) (p = 0.700) or IS and LS (p = 0.065). In stage II cancers, there was a significant difference in DFS in ES compared to IS (p < 0.001) and LS (p = 0.009). There was no significant difference between IS and LS (p = 0.478). Patients were more likely to undergo immediate reconstruction (p < 0.0001 for all stages) in later time-to-surgery groups, while patients in earlier groups were more likely to undergo breast conserving surgery. There was also no significant difference in NS at time of surgery in clinical stage 1 (p = 0.321) or stage 2 disease (p = 0.571). Delays of up to 60 days were not associated with worse outcomes. This study should reassure patients and surgeons that modest delays do not adversely affect breast cancer outcomes. This allows patients time to consider treatment and reconstruction options.

National guidelines provide breast cancer (BC) risk management recommendations based on estimated lifetime risk. Despite this specificity, it is unclear if women's risk management intentions are or are not guideline concordant. To address this knowledge gap, women at varying risk levels reported intentions for risk-reducing behaviors. Factors associated with intentions, informed by the Health Beliefs Model, were also studied.Women with elevated BC risk (N = 103) were studied and categorized by risk level: moderate (15%-20%), high (greater than or equal to 20%), or very high (BRCA1/2 positive). Participants self-reported BC susceptibility, self-efficacy, and benefits, barriers, and intentions for risk-reducing mastectomy (RRM), risk-reducing salpingo-oophorectomy (RRSO), chemoprevention, improving diet or physical activity, and reducing alcohol use.Groups significantly differed in RRSO intentions (P .01); BRCA1/2 positive women had greater intentions for RRSO. Groups did not differ in intentions for RRM, chemoprevention, or lifestyle changes (Ps .28). In hierarchical linear regression models examining Health Belief Model (HBM) factors, perceived susceptibility was associated with intentions for RRM (β = .169, P = .08). Perceived benefits was associated with intentions for RRM (β = .237, P = .02) and chemoprevention (β = .388, P .01). Self-efficacy was associated with intentions for physical activity (β = .286, P .01).Consistent with guidelines, BRCA1/2 positive women reported greater intentions for RRSO, and risk groups did not differ in intentions for lifestyle changes. Notably, women's intentions for RRM and chemoprevention were guideline discordant; groups did not differ in intentions for these behaviors. Accounting for the effects of risk group, modifiable health beliefs were also associated with risk management intentions; these may represent targets for decision support interventions.

Background Neurofibromatosis type 1 (NF1) is a cancer predisposing syndrome. Studies suggest that women

The purpose of our study was to quantitate the changes in axillary lymph node dissection (ALND), frozen section (FS), and the impact on costs after the publication of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial. We compared axillary nodal management and cost data in breast cancer patients who met Z0011 criteria and were treated with lumpectomy and sentinel lymph nodes (SLN) biopsy from 2007 to July 2013. Of 800 patients, 67 (13.5%) and 34 (12.5%) patients in the pre- and post-Z0011 era had 1-2 positive SLN. ALND decreased from 78% to 21% (p < 0.001) after publication of Z0011. The mean overall cost of SLN biopsy was $41,059 per patient, while SLN biopsy with completion ALND was $50,999 (p < 0.001). Intraoperative FS use decreased from 95% to 66% (p = 0.015). Omitting the FS decreased mean costs from $4,319 to $2,036. The application of Z0011 resulted in an overall mean cost savings of $571,653 from 2011 to July 2013. ACOSOG Z0011 significantly impacted axillary management resulting in a 20% reduction in the mean overall cost per patient by omitting ALND. In these patients, intraoperative FS analysis had poor sensitivity (56%) and doubled the cost of pathologic examination. Fewer ALND and intraoperative FS were performed after the publication of ACOSOG Z0011. Eliminating FS and ALND in patients who met Z0011 criteria, results in significant cost savings.

Background Patients with metastatic or locally aggressive cutaneous squamous-cell carcinoma (cSCC) have historically had limited and noneffective treatment options. The mainstay treatment has been surgery, which can be disfiguring and may not be technically feasible for larger lesions. Patients and Methods A retrospective review of 18 patients treated with nivolumab (n = 17) or pembrolizumab (n = 1) anti–programmed cell death protein 1 (PD-1) inhibitors for metastatic or locally advanced cSCC from March 2015 to present was performed. Results Three patients had metastatic disease, 5 patients had locally aggressive plus regional nodal disease, 8 patients had locally advanced disease, and 2 had multifocal skin disease. Seventeen patients had undergone at least 1 surgery, 12 also had received radiotherapy, 8 had disease that had failed to respond to other systemic treatments, and 2 had chronic lymphocytic leukemia. Of 18 patients treated, 14 had dramatic responses with improvement in clinical symptoms and impressive tumor reduction with equally impressive duration. Objectively, 4 patients had complete response, 10 had partial response, 3 had stable disease, and 1 patient had progression of disease. Three patients died, 1 from an ischemic cerebrovascular incident possibly related to treatment, 1 likely not related to neither treatment nor disease, and 1 due to disease progression. Therapy was otherwise well tolerated, and 10 patients currently continue to receive the therapy. Thirteen patients continue to have stable or no new disease at a median time of 12 months since the start of treatment. Conclusion PD-1 blocking agents may provide clinically meaningful and palliative therapy for patients with aggressive cSCC who are not surgical candidates.

Objective Cross-sectional data have linked gut barrier abnormalities and endotoxemia with depression, even among those without gastrointestinal symptoms. This study examined longitudinal associations between endotoxemia markers and depressive symptoms, as well as the role of inflammation in this relationship. Design At three annual visits, 315 women (n=209 breast cancer survivors, n = 106 non-cancer patient controls, M=55 years old) completed the Center for Epidemiological Studies Depression questionnaire (CES-D) and provided blood samples to assess inflammatory markers – interleukin-6, tumor necrosis factor-alpha, and C-reactive protein – and endotoxemia markers – lipopolysaccharide-binding protein (LBP), soluble CD14 (sCD14), and their ratio. Results Adjusting for key demographic variables, health behaviors, visit 1 depressive symptoms, and cancer status and treatment, women with higher visit 1 LBP and LBP/sCD14 had more depressive symptoms at the two subsequent annual visits. Illustrating the notable impact, a woman at the 75th percentile for LBP or LBP/sCD14 at visit 1 was 18 % more likely to report clinically significant depressive symptoms (CES-D ≥16) at follow-up than a woman in the lowest quartile. Cancer status and treatment type did not modulate this relationship. In contrast, visit 1 depressive symptoms did not predict endotoxemia at follow-up. A significant interaction between LBP/sCD14 and inflammatory burden suggested that visit 1 endotoxemia fueled depressive symptoms only in the context of elevated inflammation. Conclusion These results suggest that endotoxemia, combined with systemic inflammation, can drive depressive symptoms. These findings may implicate bacterial endotoxin translocation from the gut to the bloodstream in depression etiology. Interventions that reduce endotoxemia and inflammation may lessen the risk of depression.

Background Breast cancer survivors with elevated inflammation have a greater risk for cancer recurrence, premature mortality, and comorbid disease development. The psychological stress survivors experience when confronted with a breast cancer diagnosis and cancer treatment can heighten inflammation. Identifying factors that reduce stress and inflammation could lead to improvements in survivors’ long-term health. Accordingly, this study examined the health-enhancing effects of romantic relationships—a key health determinant—on breast cancer survivors’ stress and inflammation. Methods Breast cancer survivors (n = 139, stages 0–IIIC) completed a baseline visit before treatment and two follow-up visits 6 and 18 months after treatment ended. Women completed self-report questionnaires assessing their romantic relationship satisfaction and perceived stress, and they provided a blood sample for serum markers of inflammation at each visit. The longitudinal design allowed for examination within and between survivors. We conducted multilevel mediation analyses to assess how changes in survivors’ relationship satisfaction were related to changes in stress and inflammation from visit to visit (i.e., within-person effects), as well as how the average effects of relationship satisfaction were associated with average stress and inflammation levels throughout the study (i.e., between-person effects). Results At the within-person level, at visits in which survivors were more satisfied with their relationships, they also perceived less stress, which in turn was related to lower than their own average levels of serum C-reactive protein and proinflammatory cytokines (tumor necrosis factor-α, interleukin-6, and interleukin-1β). At the between-person level, survivors who had greater relationship satisfaction throughout the study had lower perceived stress, which was linked to lower levels of inflammation. Conclusion Breast cancer survivors in satisfying romantic relationships felt less stressed and in turn had lower inflammation throughout cancer treatment. This study illustrates the utility of a within-person approach to not only consider the average effects of relationship satisfaction, but also how changes in their own relationship satisfaction impact stress and inflammation over time. Our findings demonstrate important psychological and immunological pathways through which satisfying relationships may promote breast cancer survivors’ long-term health.

A meta-analysis of 22 randomized trials accrued from 1964 to 1986 demonstrated significantly higher rates of locoregional failure (LRF) and breast-cancer mortality in women with 1–3 positive nodes without postmastectomy radiotherapy (PMRT) after mastectomy (mast.). Recent data demonstrate that PMRT reduces distant metastases (DM) in women with pN1 disease. The challenge today is whether all patients with pathologic T1-2pN1 disease have similar substantial LRF/DM risk that routinely warrants PMRT. We reviewed patients with pT1-2N1 breast cancer treated with mast. ± adjuvant systemic therapy without PMRT from 2000 to 2013. The endpoints were LRF and DM rates, estimated by cumulative incidence method. We identified 468 patients with median follow-up of 6.3 years. Most (71%) were estrogen receptor/progesterone receptor + human epidermal growth factor receptor 2 (HER2). There were 269 patients with 1+ node, 140 patients with 2+ nodes, and 59 patients with 3+ nodes. The 6-year LRF/DM rates were 4.1%/8.4%. Patients with 1+, 2+, and 3+ nodes had 6-year LRF of 2.3, 5.1 and 8.9%, respectively (p = 0.13). The 6-year DM rate was higher in patients with 3+ nodes versus 1–2+ nodes: 15.7% versus 7.4% (p = 0.02). Several subgroups had low 6-year LRF and DM rates, including T1/1+ node (0.8%/4.1% LRF/DM) and micrometastases (0%/5.8% LRF/DM). Patients with pT1-2pN1 represent a heterogeneous group with a wide range of LRF/DM rates. In particular, patients with pT1 tumors and 1 + LN, and patients with micrometastases, had low event rates. These groups would derive small absolute reductions in LRF and DM with addition of PMRT, underscoring the importance of patient selection for PMRT in pT1-2pN1 breast cancer.

Obesity and cancer are two common diseases in the United States. Although there is an interaction of obesity and cancer, little is known about surgeon perceptions and practices in the care of obese cancer patients. We sought to characterize perceptions and practices of surgical oncologists regarding the perioperative care of obese patients being treated for cancer. A cross-sectional survey was designed, pilot tested, and utilized to assess perceptions and practices of surgeons treating cancer patients. Surgical oncologists were identified using a commercially available database, and Qualtrics® was used to distribute and manage the survey. Statistical analyses were completed by using SPSS. Of the 1731 electronic invitations, 172 recipients initiated the survey, and 157 submitted responses (91.2%). Many surgeons (65.7%) believed that obese patients are more likely to present with more advanced cancers and were more likely than system factors to explain this delayed treatment [t(87) = 4.84; p

Family history is a well-recognized risk factor for the development of breast and gynecologic cancer. It is thought that hereditary cases account for 5–10% of all cancers. A number of well-established, highly penetrant syndromes such as Lynch syndrome and hereditary breast and ovarian cancer syndrome account for the vast majority of the hereditary cases. A number of other moderate-risk genes associated with familial syndromes have also been described. The identification of these additional genes has greatly expanded testing options; however, less is known about risk and management for these more recently described genes. This chapter describes the hereditary syndromes associated with breast and gynecologic malignancies and provides risk-reduction recommendations when available. The criteria for genetic testing, methods of genetic testing, and application of results are reviewed.

A descriptive retrospective study was performed using two separate user cohorts to determine the effectiveness of Family HealthLink as a clinical triage tool.Cohort 1 consisted of 2,502 users who accessed the public website. Cohort 2 consisted of 194 new patients in a Comprehensive Breast Center setting. For patient users, we assessed documentation of family history and genetics referral. For all users seen in a genetics clinic, the Family HealthLink assessment was compared with that performed by genetic counselors and genetic testing outcomes.For general public users, the percentage meeting high-risk criteria were: for cancer only, 22.2%; for coronary heart disease only, 24.3%; and for both diseases, 10.4%. These risk stratification percentages were similar for the patient users. For the patient users, there often was documentation of family history of certain cancer types by oncology professionals, but age of onset and coronary heart disease family history were less complete. Of 142 with high-risk assignments seen in a genetics clinic, 130 (91.5%) of these assignments were corroborated. Forty-two underwent genetic testing and 17 (40.5%) had new molecular diagnoses established.A significant percentage of individuals are at high familial risk and may require more intensive screening and referral. Interactive family history triage tools can aid this process.Genet Med 17 6, 493-500.

Background and objectives Head and neck (HN) cutaneous melanoma is associated with worse disease-free survival compared to non-HN cutaneous melanoma, possibly due to inadequate staging. We aim to determine if a higher yield of sentinel lymph nodes (SLNs) affected rates of sentinel lymph node biopsy (SLNB) positivity. Methods Two Cancer Registries were used to identify patients who underwent SLNB for HN melanoma. A false negative (FN) was defined by nodal recurrence after negative SLNB. Results Out of 333 patients who underwent SLNB, 20% (n = 69) had a positive SLN with a FN rate of 6.3%. Those with three or more SLNs had a higher rate of SLN positivity (23.8% [17.5-29.9% CI] vs 16.4% [10.7-23.6% CI]), a lower FN rate (16.7% [10.2-21.2% CI] vs 35.3% [27.1-42.9% CI]), and higher sensitivity (83.3% [82.59-84.09% CI] vs 65.7% [64.87-66.53% CI]) compared to those with one or two SLNs. Of patients in Group 1 (one or two SLNs) with a positive SLN who underwent completion lymph node dissection (20/23), 47% (33-61% CI) had one or more positive non-sentinel nodes compared to 29% (16-51%) of patients in Group 2 (three or more SLNs) (42/46). Conclusion In HN melanoma cases in which multiple nodes are identified, removal of all SLNs will more adequately stage patients.

Sentinel-lymph-node biopsy is associated with increased melanoma-specific survival (i.e., survival until death from melanoma) among patients with node-positive intermediate-thickness melanomas (1.2 to 3.5 mm). The value of completion lymph-node dissection for patients with sentinel-node metastases is not clear. In an international trial, we randomly assigned patients with sentinel-node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma-specific survival. Secondary end points included disease-free survival and the cumulative rate of nonsentinel-node metastasis. Immediate completion lymph-node dissection was not associated with increased melanoma-specific survival among 1934 patients with data that could be evaluated in an intention-to-treat analysis or among 1755 patients in the per-protocol analysis. In the per-protocol analysis, the mean (±SE) 3-year rate of melanoma-specific survival was similar in the dissection group and the observation group (86±1.3% and 86±1.2%, respectively; P=0.42 by the log-rank test) at a median follow-up of 43 months. The rate of disease-free survival was slightly higher in the dissection group than in the observation group (68±1.7% and 63±1.7%, respectively; P=0.05 by the log-rank test) at 3 years, based on an increased rate of disease control in the regional nodes at 3 years (92±1.0% vs. 77±1.5%; P

BACKGROUND. Sentinel lymph node biopsy (SLNB) is routinely performed for primary cutaneous melanomas; however, limited data exist for SLNB after locally recurrent (LR) or in-transit (IT) melanoma. METHODS. Data from three centers performing SLNB for LR/IT melanoma (1997 to the present) were reviewed, with the aim of assessing (1) success rate; (2) SLNB positivity; and (3) prognostic value of SLNB in this population. RESULTS. The study cohort included 107 patients. Management of the primary melanoma included prior SLNB for 56 patients (52%), of whom 10 (18%) were positive and 12 had complete lymph node dissections (CLNDs). In the present study, SLNB was performed for IT disease (48/107, 45%) or LR melanoma (59/107, 55%). A sentinel lymph node (SLN) was removed in 96% (103/107) of cases. Nodes were not removed for four patients due to lymphoscintigraphy failures (2) or nodes not found during surgery (2). SLNB was positive in 41 patients (40%, 95% confidence interval (CI) 31.5-50.5), of whom 35 (88%) had CLND, with 13 (37%) having positive nonsentinel nodes. Median time to disease progression after LR/IT metastasis was 1.4 years (95% CI 0.75–2.0) for patients with a positive SLNB, and 5.9 years (95% CI 1.7–10.2) in SLNB-negative patients (p = 0.18). There was a trend towards improved overall survival for patients with a negative SLNB (p = 0.06). CONCLUSION. SLNB can be successful in patients with LR/IT melanoma, even if prior SLNB was performed. In this population, the rates of SLNB positivity and nonsentinel node metastases were 40% and 37%, respectively. SLNB may guide management and prognosis after LR/IT disease.

Melanoma remains the leading cause of skin cancer–related deaths. Surgical resection and adjuvant therapies can result in disease-free intervals for stage III and stage IV disease; however, recurrence is common. Understanding microRNA (miR) dynamics following surgical resection of melanomas is critical to accurately interpret miR changes suggestive of melanoma recurrence. Plasma of 6 patients with stage III (n = 2) and stage IV (n = 4) melanoma was evaluated using the NanoString platform to determine pre- and postsurgical miR expression profiles, enabling analysis of more than 800 miRs simultaneously in 12 samples. Principal component analysis detected underlying patterns of miR expression between pre- vs postsurgical patients. Group A contained 3 of 4 patients with stage IV disease (pre- and postsurgical samples) and 2 patients with stage III disease (postsurgical samples only). The corresponding preoperative samples to both individuals with stage III disease were contained in group B along with 1 individual with stage IV disease (pre- and postsurgical samples). Group A was distinguished from group B by statistically significant analysis of variance changes in miR expression ( P < .0001). This analysis revealed that group A vs group B had downregulation of let-7b-5p, miR-520f, miR-720, miR-4454, miR-21-5p, miR-22-3p, miR-151a-3p, miR-378e, and miR-1283 and upregulation of miR-126-3p, miR-223-3p, miR-451a, let-7a-5p, let-7g-5p, miR-15b-5p, miR-16-5p, miR-20a-5p, miR-20b-5p, miR-23a-3p, miR-26a-5p, miR-106a-5p, miR-17-5p, miR-130a-3p, miR-142-3p, miR-150-5p, miR-191-5p, miR-199a-3p, miR-199b-3p, and miR-1976. Changes in miR expression were not readily evident in individuals with distant metastatic disease (stage IV) as these individuals may have prolonged inflammatory responses. Thus, inflammatory-driven miRs coinciding with tumor-derived miRs can blunt anticipated changes in expression profiles following surgical resection.

Background: Cancer survivors often experience cognitive difficulties after treatment completion. Although chemotherapy enhances risk for cognitive problems, it is likely only one piece of a complex puzzle that explains survivors’ cognitive functioning. Loneliness may be one psychosocial risk factor. The current studies included both subjective and objective cognitive measures and tested whether lonelier breast cancer survivors would have more concentration and memory complaints and experience more concentration difficulties than their less lonely counterparts. Methods: The relationship between loneliness and cognitive function was tested among three samples of breast cancer survivors. Study 1 was a sample of breast cancer survivors (n=200) who reported their concentration and memory problems. Study 2a was a sample of breast cancer survivors (n=185) and noncancer controls (n=93) who reported their concentration and memory problems. Study 2b was a subsample of Study 2a breast cancer survivors (n=22) and noncancer controls (n=21) who completed a standardized neuropsychological test assessing concentration. Results: Studies 1 and 2a revealed that lonelier women reported more concentration and memory problems than less lonely women. Study 2b utilized a standardized neuropsychological continuous performance test and demonstrated that lonelier women experienced more concentration problems than their less lonely counterparts. Conclusions: These studies demonstrated that loneliness is linked to concentration and memory complaints and the experience of concentration problems among breast cancer survivors. The results were also highly consistent across three samples of breast cancer survivors. These data suggest that loneliness may be a risk factor for cognitive difficulties among cancer survivors. Copyright © 2014 John Wiley & Sons, Ltd.

Objective Breast cancer is the most common cancer among women worldwide. Given the advances in extending survival, the number of recently diagnosed breast cancer patients and longer-term breast cancer survivors is growing. The goals of this study were to better understand (1) perceptions of provider cancer recurrence risk communication, (2) perceived risk of breast cancer recurrence in cancer patients and survivors, and (3) accuracy of perceived risk. Methods A survey was conducted on women with a prior breast cancer (n = 141). Results Approximately 40% of women perceived that providers had not talked about their breast cancer recurrence risk; although only 1 person reported not wanting a physician to talk to her about her risk. Women were largely inaccurate in their assessments of risk. Greater worry, living in a rural area, and longer time since diagnosis were associated with greater inaccuracy. Women tended to think about distal recurrence of cancer as often of local recurrence. Conclusions Perceived risk of breast cancer recurrence was inaccurate, and patients desired more communication about recurrence risk. Practice implications Consistent with findings from other studies, greater efforts are needed to improve the communication of cancer recurrence risk to patients. Attention should be paid to those from rural areas and to distal cancer recurrence in women with a previous history of breast cancer.

The ataxia-telangiectasia mutated (ATM) gene encodes a protein kinase involved in DNA repair. Heterozygotic carriers are at an increased risk of developing breast cancer. As the use of genetic testing increases, identification of at-risk patients will also increase. The aim of this study is to review two cases of heterozygous ATM mutation carriers and review the literature to clarify the cancer risks and suggested management for breast surgeons who will be intimately involved in the care of these patients.

Background After appropriate initial therapy for patients with stage II-III melanoma, there is no consensus regarding surveillance. Thus, follow-up is highly variable among institutions and individual providers. The National Comprehensive Cancer Network recommends routine clinical examination and consideration of imaging for stage IIB-IIIC every 3-12 mo with no distinction between stages. Detection of recurrence is important as novel systemic therapies and surgical resection of recurrence may provide survival benefits. Methods We retrospectively reviewed 369 patients with stage II and III melanoma treated at Ohio State University from 2009-2015, who underwent surgery as primary therapy. Two hundred forty-seven patients who were followed for a minimum of 6 mo after surgical resection to achieve no evidence of disease status (NED) were included in this analysis. One hundred twenty-two were lost to follow-up after surgery and were excluded. Results The rate of recurrence for stage IIA/IIB patients was 11% (14/125). Eleven of the 14 (79%) recurrences were detected by clinical symptoms or physical examination. Thirty-nine percent (49/125) of stage IIA or IIB patients were followed by clinical examination only, whereas 61% (76/125) were followed with at least two serial chest x-rays. The median time to first chest x-ray after NED status was 4.7 mo (n = 76), median time to second chest x-ray after NED status was 12.7 mo (n = 76), and 66% (50/76) continued to have additional serial chest x-rays. At median follow-up of 35 mo for the 125 patients with stage IIA/IIB, there was no difference in survival between those followed clinically (95% [95% CI: 0.88-0.99]) versus those followed with at least two serial x-rays (96% [95% CI: 0.89-0.98]). For stage IIC/IIIA-C patients, recurrence was detected in 23% (28/122) at median follow-up 31.2 mo. Fifty percent of recurrences were detected by imaging in asymptomatic patients, whereas 50% (14/28) had recurrence detected on imaging associated clinical findings. Eighty-seven percent (106/122) of stage IIC/IIIA-C patients were followed with at least two serial whole body positron emission tomography/computed tomography (CT) scans or whole body CT scans plus brain magnetic resonance imaging; median time between NED status and second scan was 10.3 mo. Of stage IIC/IIIA-C patients with recurrence, 57% (16/28) went on to surgical resection of the recurrence, whereas 11 (39%) patients received B-RAF inhibitor therapy, immune blockade therapy, or combination therapy. Conclusions For stage IIA and IIB melanoma, surveillance chest x-rays did not improve survival compared to physical examination alone. However, for stage IIC and IIIA-C melanoma, where the recurrence rates are higher, routine whole body imaging detected 50% of recurrences leading to additional surgery and/or treatment with novel systemic therapies for the majority of patients. Detection of melanoma recurrence is important and specific substage should be used to stratify risk and define appropriate follow-up.

Purpose The sequelae of cancer treatment may increase systemic inflammation and create a phenotype at increased risk of functional decline and comorbidities, leading to premature mortality. Little is known about how this trajectory compares with natural aging among peers of the same age without cancer. This longitudinal study investigated proinflammatory cytokines and comorbidity development over time among breast cancer survivors and a noncancer control group. Methods Women (N = 315; 209 with breast cancer and 106 in the control group) were recruited at the time of their work-up for breast cancer; they completed the baseline questionnaire, interview, and blood draw (lipopolysaccharide-stimulated production of interleukin [IL] -6, tumor necrosis factor-α, and IL-1β). Measures were repeated 6 and 18 months after primary cancer treatment (cancer survivors) or within a comparable time frame (control group). Results There were no baseline differences in comorbidities or cytokines between survivors and the control group. Over time, breast cancer survivors had significantly higher tumor necrosis factor-α and IL-6 compared with the control group. Survivors treated with surgery, radiation, and chemotherapy accumulated a significantly greater burden of comorbid conditions and suffered greater pain associated with inflammation over time after cancer treatment than did the control group. Conclusion Survivors who had multimodal treatment had higher cytokines and comorbidities, suggestive of accelerated aging. Comorbidities were related to inflammation in this sample, which could increase the likelihood of premature mortality. Given that many comorbidities take years to develop, future research with extended follow-up beyond 18 months is necessary to examine the evidence of accelerated aging in cancer survivors and to determine the responsible mechanisms.

As surgeons who care for patients with breast cancer, the possibility of a cancer diagnosis being related to a hereditary predisposition is always a consideration. Not only are we as surgeons always trying to identify these patients and families but also we are often asked about a potential hereditary component by the patients and their family members. It is therefore critical that we accurately assess patients to determine who may benefit from genetic testing. Importantly, the potential benefit for identifying a hereditary breast cancer extends beyond the patient to other family members and the risk may not be only for the development of breast cancers, but for other cancers as well. This review was written from the perspective of a surgeon with additional training in cancer genetics in an effort to provide a unique perspective on the issue and feel that a review of some of the more practical considerations is important.

Objective A cancer diagnosis provokes significant levels of emotional distress, with intrusive thoughts being the most common manifestation among breast cancer survivors. Cancer-related intrusive thoughts can take the form of emotional memories, flashbacks, nightmares, and intrusive images. Emotional arousal after a severe life stressor prolongs adrenergic activation, which in turn may increase risk for post-traumatic symptomatology. However, antihypertensive beta-blockers block adrenergic activation and are known to reduce traumatic memories and related psychological distress. Thus, the current study examined the association between beta-blocker use and the severity of cancer-related intrusive thoughts and related symptoms following a cancer diagnosis. Methods The 174 breast and 36 female colorectal cancer patients who had recently undergone diagnostic screening or biopsy included 39 beta-blocker users and 171 non-users. Prior to any cancer treatment including surgery, participants completed questionnaires that included the Impact of Events Scale and the Center for Epidemiological Studies Depression Scale. Analyses controlled for age, education, cancer stage, cancer type, days since diagnosis, marital status, depression, and comorbidities. Results Although the high rates of cancer-related distress in this sample were similar to those of other studies with recently diagnosed patients, beta-blocker users endorsed 32% fewer cancer-related intrusive thoughts than non-users. Conclusions Recently diagnosed cancer patients using beta-blockers reported less cancer-related psychological distress. These results suggest that beta-blocker use may benefit cancer patients' psychological adjustment following diagnosis, and provide a promising direction for future investigations on the pharmacological benefits of beta-blockers for cancer-related distress. Copyright © 2012 John Wiley & Sons, Ltd.

Fatigue is a notable clinical problem in cancer survivors, and understanding its pathophysiology is important. The current study sought to determine biomarkers of fatigue that exist before cancer treatment. Relationships between the expression of latent Epstein–Barr virus (EBV) and cytomegalovirus (CMV) and fatigue were examined in 158 women newly diagnosed with breast cancer or awaiting a positive diagnostic result. Higher CMV antibody titers, but not EBV antibody titers, were associated with a greater likelihood of being fatigued. Associations between fatigue and higher CMV antibody titers remained after controlling for alcohol use, smoking, comorbidities, depressive symptoms, age, BMI, cancer stage, and sleep problems. More sleep problems and higher levels of depressive symptoms were also associated with a greater likelihood of being fatigued. CMV antibody titers, but not EBV antibody titers, were associated with higher levels of C-reactive protein (CRP), but CRP was not associated with fatigue. When the cellular immune system is compromised, reactivation of latent herpesviruses may fuel chronic inflammatory responses. Prior work has suggested that fatigue may be related to inflammation and its associated sickness behaviors; accordingly, our findings may be tapping into this same physiological substrate.

Introduction: Breast cancer is the leading cause of cancer, and the second leading cause of cancer death in women. Due to advances in medicine, the 10 year survival rate is 80%, resulting in a large and growing number of breast cancer survivors. Definitions of cancer survivorship from a number of professional organizations and researchers vary, but the research is scant on the meaning of cancer survivorship to people with and without a prior cancer history. Methods: Two studies were conducted (1) to compare individuals with and without a prior personal cancer diagnosis in terms of those who identified as survivors vs. those who did not identify as survivors and (2) to explore explanations of those with and without a prior personal cancer for the term cancer survivor. In Study 1, individuals were surveyed at cancer-themed community health fairs. In Study 2, women were surveyed at a breast oncology clinic. Results: In Study 1 comparing those with and without a prior cancer diagnosis, prior cancer history was the best predictor of survivorship identity, and only three individuals without a prior cancer history included family and friends as survivors. In Study 2 of those with a personal history, longer time since diagnosis, type of cancer (ductal), and comparative risk (higher) were associated with survivor identity. Conclusion: Completion of treatment was seen as a ‘rite of passage’, and thus, may be seen as a shift from the patient identity, which may have negative connotations, to the positive identity of survivor. Implications: Definitions of survivorship vary considerably, and caution should be used when applying the term to those who have no prior personal cancer diagnosis and to those who have had a more recent cancer diagnosis with a more severe disease course.

An increasing trend in the use of contralateral prophylactic mastectomy (CPM) for the treatment of unilateral breast cancer has been observed nationally. The purpose of this study was to confirm this trend and to identify differences between the groups that chose unilateral mastectomy alone or with CPM. A prospectively maintained breast cancer database was retrospectively reviewed. Age, histologic grade, stage, education, family history, tumor receptor status, and use of immediate reconstruction were evaluated. Statistical analysis was performed by Fisher’s exact test, χ2 test, and Student’s t-test. Between 1998 and 2007, a total of 1639 women who selected UM and 201 who had UM and CPM for unilateral breast cancer were identified. An increasing trend in CPM was observed (6.5% in 1999 vs. 16.1% in 2007). The CPM group was significantly younger (mean age 47.8 vs. 55.1 years, P

Background Although breast cancer is relatively common, only about 5% of cases are due to inheritance of highly penetrant cancer susceptibility genes. The majority of these are caused by mutations in the BRCA1 and BRCA2 genes, which are also associated with an increased risk of ovarian cancer. Increased surveillance, chemoprevention, and prophylactic surgeries are standard options for the effective medical management of mutation carriers. However, optimal management of female carriers who choose to undergo prophylactic surgeries is still poorly understood. Methods The authors provide an overview of the current literature regarding medical management options for women carriers of BRCA1 and BRCA2 gene mutations and the implications for those individuals who have chosen to undergo prophylactic surgeries. Results BRCA mutation carriers who opt for prophylactic surgeries are still at risk for development of malignancy, and appropriate monitoring is warranted. Conclusions There are limited data on the appropriate medical management for BRCA mutation carriers after prophylactic surgeries. However, a management plan can be extrapolated from the general management recommendations for surveillance and other risk-reducing strategies in BRCA-positive individuals.

Management algorithms for invasive and non-invasive ductal and lobular breast carcinomas are well-established. Because of their very nature, rare histologic types of primary breast cancers are not represented in practice guidelines and thus present a challenge to the practicing clinician who must make recommendations for surgical treatment, axillary staging, and adjuvant therapy, as well as counsel patients as to their expected disease course and prognosis. Herein, case reports and published series of rare types of primary breast cancer including adenoid cystic, mucoepidermoid, metaplastic, squamous, neuroendocrine, encysted papillary, and micropapillary types will be reviewed to provide a basis for treatment planning for patients presenting with these rare primary breast malignancies.

With the improvements in imaging techniques that have allowed the earlier detection of smaller breast cancers and the desire for improvements in cosmetic outcome, a number of minimally invasive techniques for the treatment of early stage breast cancers are being investigated. Ablative therapies, including laser ablation, focused ultrasound, microwave ablation, radiofrequency ablation, and cryoablation, have been described. All of these techniques have shown promise in the treatment of small cancers of the breast; however, additional research is needed to determine the efficacy of these techniques when they are used as the sole therapy and to determine the long-term local recurrence rates and survival associated with these treatment strategies.

BACKGROUND Radiofrequency ablation (RFA) is gaining acceptance as a treatment modality for several tumor types. However, its use in patients with breast carcinoma remains investigational. The current study was undertaken to determine the feasibility of treating small breast malignancies with RFA and to evaluate the postablation magnetic resonance imaging scans (MRI) and histologic findings. METHODS Patients with core-needle biopsy–proven invasive carcinoma (< 2 cm in greatest dimension) underwent ultrasound-guided RFA under local anesthesia. Surgical excision was undertaken 1–3 weeks later. All patients had breast MRI scans performed before ablation and repeated within 24 hours of surgery. RESULTS Ten patients completed the treatment and experienced minimal or no discomfort. The mean tumor size was 1.2 cm (range, 0.8–1.6 cm). The mean time required for ablation was 13.8 minutes (range, 7–21 minutes). There were no treatment-related complications other than minimal breast ecchymosis. A pre-RFA MRI scan showed enhancing tumors in 9 of 10 (90%) patients. A post-RFA MRI scan revealed no residual lesion enhancement in 8 of these 9 patients (89%), and the zone of ablation was demonstrated in all patients. One patient had residual enhancement anteriorly consistent with residual tumor, which was confirmed histologically. Evaluation of the remaining ablated lesions revealed a spectrum of changes ranging from no residual tumor to coagulation necrosis with recognizable malignant cells. Immunostains for cytokeratin 8/18 were negative in these recognizable malignant cells. CONCLUSIONS RFA of small breast malignancies can be performed under local anesthesia in an office-based setting. A postablation MRI scan appears to predict histologic findings, although tumor viability needs to be assessed in a long-term study. Cancer 2003;98:1369–76. © 2003 American Cancer Society. DOI 10.1002/cncr.11642

Tumor necrosis factor-alpha (TNF-alpha) is a well-documented central inflammatory mediator in sepsis. Specific polymorphisms of the TNF-alpha and TNF-beta genes (TNF2 and LTA + 250, respectively) have been suggested to correlate with higher mortality in septic shock. This study sought to determine whether these polymorphisms of the TNF-alpha and -beta genes are associated with an increased risk of infection in an at-risk surgical intensive care population.Forty-four consecutive patients with systemic inflammatory response syndrome were enrolled prospectively in the study. Genomic DNA was isolated from whole blood samples using standard phenol/chloroform extraction techniques. Specific fragments including the polymorphic sites of each gene were amplified by polymerase chain reaction, and restriction enzyme digestions were performed. Genotypes were determined by gel electrophoresis and confirmed by direct sequencing.Eighty-six percent of the patients were TNF1 homozygotes (G:G at -308 of the TNF-alpha promoter region), whereas 9% of the patients were homozygous for TNF2 (A:A). There was no difference in the incidence of sepsis, septic shock, or mortality between patients bearing the various alleles. Only 13.6% of the patients exhibited the G:G alleles for TNF-beta, whereas the homozygous A:A was present in 45.4% of the patients.The presence of the A allele at these polymorphic sites did not predispose critically ill surgical patients to either infection or septic shock.